Quantitative Systems Pharmacology‐Based Digital Twins Approach Supplements Clinical Trial Data for Enzyme Replacement Therapies in Pompe Disease
Abstract
Pompe disease is a rare, progressive neuromuscular disease caused by deficient lysosomal glycogen degradation, and includes both late‐onset (LOPD) and severe infantile‐onset (IOPD) phenotypes. Due to very small patient numbers in IOPD and the high phenotypic heterogeneity observed in this population, a quantitative systems pharmacology (QSP)‐based “digital twin” approach was developed to perform an in silico comparison of the efficacy of avalglucosidase alfa vs. the standard of care, in a virtual population of IOPD patients. A QSP model was developed that represents key elements of Pompe disease pathophysiology, including tissue glycogen accumulation and the elevation of the biomarker urine Hex4 in both LOPD and IOPD patients. In this approach, the QSP model was used to generate digital twins of each IOPD patient enrolled in the avalglucosidase alfa clinical program, considering their respective disease burden, demographics, and treatment history. This virtual cohort supplemented clinical observations by simulating and comparing tissue glycogen and urine Hex4 following avalglucosidase alfa treatment vs. the standard of care. The digital twin analysis supports the interpretation that the enhanced reduction in urine Hex4 observed following avalglucosidase alfa treatment is attributable to greater tissue glycogen clearance. Overall, this study provides mechanism‐based insight into avalglucosidase alfa efficacy across the phenotypic spectrum of Pompe disease and demonstrates the…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
Read the paper
Related studies
- Improving the translation of search strategies using the Polyglot Search Translator: a randomized controlled trial
- Nutritional, Physical, Cognitive, and Combination Interventions and Frailty Reversal Among Older Adults: A Randomized Controlled Trial
- Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study
- A randomized, controlled trial of oral propranolol in infantile hemangioma
- Clinical phenotypes of delirium during critical illness and severity of subsequent long-term cognitive impairment: a prospective cohort study
- Increased physical activity improves sleep and mood outcomes in inactive people with insomnia: a randomized controlled trial
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.